The goal of this project is to identify breast cancer risk factors (hormonal and nonhormonal, environment and diet, carcinogens and anticarcinogens) and markers of inheritable susceptibility. A case- control study incorporating extensive epidemiological data has previously been conducted; blood clots and sera have been stored. Genetic susceptibilities will be determined in premenopausal and postmenopausal cases and controls (population-based age-matched (n=900). DNA has been extracted from 500 post-menopausal cases and controls. Genotyping for glutathione-S-transferase M1, CYP1A1, CYP2D6, CYP2E1 and N- acetyltransferase will be performed. The p53 tumor suppressor gene mutational spectra will be determined in women with histologically proven cancer from whom blood is also available, but only for informative cases, identified by single-stranded conformational polymorphism analysis and immunohistochemical staining. Informative cases categorized by mutation and a hypothesized chemical etiology will be compared to persons with other types of p53 tumor suppressor gene mutations (four for each case) and also to controls without cancer (ten for each case). Human sera also is being examined for polychlorinated biphenyls, anti-p53 antibodies and anti-polycyclic aromatic hydrocarbon-DNA adducts. Odds ratios and logistic regression will address the association of genetic polymorphisms and exposures as a risk for p53 mutation and breast cancer, adjusting for other risk factors. We also will examine effect modification for other risk factors by genetic polymorphisms.